Passive Stretch Improves Insulin-stimulated Glucose Transport Together With Downregulation Of TXNIP In Rat Soleus Muscle

Abstract

PURPOSE: Although passive stretch is known to stimulate muscle glucose transport independently of insulin action, it is unclear whether stretch increases susceptibility of glucose transport to insulin and improves insulin resistance in skeletal muscles. Therefore, we examined the effect of stretch on insulin-stimulated glucose transport in insulin resistant soleus muscles of immobilized rats. In addition, we examined the possibility that stretch decreases protein expression of TXNIP which is known to be a key negative regulator of insulin signaling. METHODS: Rats were divided into non-immobilized control and immobilized groups. Non-immobilized control rats were allowed to move freely in their cages. Immobilized rats were anesthetized and their both hindlimbs were immobilized for 6 h. Unilateral soleus muscles of immobilized rats were shortened by plantarflexing the ankle joint throughout 6 h immobilization. Contralateral muscles were stretched for 1 h by dorsiflexing the ankle joint following 5 h shortening by plantarflexing. We measured basal and insulin (50μU/ml) stimulated 2-deoxyglucose (2DG) uptake rate in isolated soleus muscles. Moreover, TXNIP protein expression was evaluated in these muscles. RESULTS: Although insulin (50μU/ml) increased glucose transport by 1.9-fold in soleus muscles of non-immobilized control rats (p<0.05), insulin did not significantly increase glucose transport in shortened muscles of immobilized rats. This result shows that insulin resistance is induced in these shortened muscles. On the other hand, 1 h passive stretch restored insulin resistance of glucose transport in muscles of immobilized rats (insulin-stimulated 2DG uptake in control, 3.12±0.29; shortened, 1.73±0.17; stretched, 3.04±0.31μmol/g muscle/20min). In addition, TXNIP protein was increased in shortened muscles of immobilized rats as compared with muscles of control rats (p<0.05). Moreover, elevated TXNIP expression in these muscles was returned to control level after 1 h passive stretch (TXNIP in control, 100±9; shortened, 166±8; stretched, 107±9 arbitrary units). CONCLUSIONS: Passive stretch improves insulin-stimulated glucose transport in insulin-resistant soleus muscles of immobilized rats. This may be due to stretch-induced downregulation in TXNIP protein expression.